Pharmacologically significant biological products for research and therapy are manufactured largely using various cell culture technologies (Chu et al., “Current Opinion in Biotechnology” (2201) 12: 180-187). Monoclonal antibodies, recombinant proteins/peptides including vaccines, produced by such technologies, are currently on the market or in active, phased development world wide. World wide demand for large scale cell culture production, therefore, continues to increase.
Currently, the industry standard method for large scale cell culture is suspension-perfusion technology. Prior art devices and methods disclose interrupted exposure to oxygenation by continually and alternately the dipping of cells in out of culture media or moving cells in and out of submersion by a moving belt. These methods and devices compromise between minimizing shear stress on the cells and oxygenation. A few examples of current methods used for cell culture are described briefly below.
U.S. Pat. No. 5,256,298 issued Oct. 26, 1993 to Paul E. Powell, discloses an device and method which use a continuous, moving belt of resilient, open-cell foam polymer to establish a turbulent flow of fluids. The belt moves alternately bulk liquid and gas phases to enable mass transfer polymer surface and the liquid and/or gas as a consequence of compression and release of the belt.
United States Patent No. 20040058434 issued Mar. 25, 2004 to Philippe Gault, describes a reactor for cell and tissue culture which involves mechanical stimulation of tissues or cells and supply of nutrients by way of a culture medium suitable for structural tissues. An optimum levels of nutrient and oxygen supply necessary for growth of cells or tissues, is achieved by reducing the density of cells and the preparation of implants in a variety of forms, compositions and applications.
U.S. Pat. No. 7,033,823 issued Apr. 25, 2006, to King-Ming titled “Chang Cell-cultivating device” teaches a cell culture method and device where a growth substrate capable of providing a large surface area for cell adhesion. By intermittently and periodically providing sufficient oxygen and nutrients to the cells without causing cell death, it also functions also as an oxygenator, a depth filter and a static mixer to maximize the production of cellular products. The optimum levels of oxygenation and nutrient are regulated by controlling the amount of culture medium that comes into contact with the growth substrate means.
United States Patent Application No. filed Mar. 25, 2005, by Code Kind and Philippe Gault, titled “Bioreactor For Tissue Cultivated In The Form Of a Thin Layer and Uses Thereof” teaches cell culture methods that grow cells on a thin film held between two plates. This method is specifically designed for tissue implants, but not for the growth of cells by direct exposure to liquid/air interface.
All these methods suffer from major disadvantages in that they have to continuously compromise between sufficient movement of culture media across cell membranes to provide them nutrients for sufficient growth and, at the same time provide sufficient O2/CO2 gas exchange rates, without limiting rate of movement of these elements, to minimize shear-stress to the cells. This is a serious dilemma, and currently “dealt with” by reducing cell density to levels that are supported by the limited gas exchange rates. They are not suitable for large scale production as they are not directly scalable.
It would be highly desirable to have a bioreactor device and method available that provides maximal oxygen transfer to all cells in the culture in a substantially equivalent manner while, at the same time, supplies sufficient nutrients for cell growth in high density, convenient product harvesting and ready scalability.
It is thus an object of the present invention to provide a high performance and high density bioreactor for cell growth and culture.
It is another object of this invention to provide a method and device for cell culture where the cells are continuously, rather than intermittently, bathed in a culture medium with zero shear-stress, while simultaneously and continuously supplied essential nutrients and exposed to optimal O2/CO2 gas exchange.
It is an object of the present invention to provide a novel bioreactor for the culture of cells without having to immerse the cells in the growth medium.
Another object of the present invention is to provide a bioreactor for cell culture wherein the cells are continuously and simultaneously fed and aerated to achieve maximum growth in a relatively short time.
Yet another object of the present invention is to provide a bioreactor which is directly scalable to workable proportions.
Yet another object to provide an “accelerated wicking” process for the distribution of the growth medium across the surface of cell support matrix.
Additional objects, advantages and novel features of the invention will be set forth in part in the description and drawings which follow, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.